Systems and methods for treatment of pulmonary edema

ABSTRACT

Systems, methods, and devices are provided for the treatment of edema. In one aspect a method for implanting an indwelling catheter within a vein of a patient is provided. The catheter can extend from a position upstream of at least one outflow port of a duct of the lymph system to a terminal position downstream of the at least one outflow port. In use, a first restriction can be created within the vein proximal to a distal region of the catheter. The first restriction can define a localized low pressure zone distal of the restriction and within a portion of the vein housing the catheter. The low pressure zone can be adjacent to the at least one outflow port to enable fluid to pass from the at least one lymph duct outflow port into the vein.

CROSS REFERENCE

The present application is a continuation of U.S. patent applicationSer. No. 15/471,842 entitled “System And Method For Treatment ofPulmonary Edema” filed Mar. 28, 2017, which is a continuation of U.S.patent application Ser. No. 14/625,930 entitled “System And Method ForTreatment of Pulmonary Edema” filed Feb. 19, 2015, which claims priorityto U.S. Provisional Patent Application No. 62/006,206 entitled “SystemAnd Method For Treatment of Pulmonary Edema” filed Jun. 1, 2014, whichare hereby incorporated by reference in their entireties.

FIELD

The present disclosure relates to surgical systems, devices and methodsreducing pulmonary edema in a patient.

BACKGROUND

The lymphatic system is part of the circulatory system in conjunctionwith the arterial and venous systems. A primary function of thelymphatic system is to drain excessive interstitial fluid back into thevenous system at two main locations: the thoracic duct and the lymphaticduct, which drain into the left and right subclavian veins,respectively.

Under normal circulatory conditions of the arterial and venous systemsthe interstitial fluid volume balance is maintained and the lymph fluidis cleared back through the lymphatic system. In pathological conditionssuch as Acute Cardiogenic Pulmonary Edema, the capillary hydrostaticpressure and the venous pulmonary pressure can become elevated and fluidflows excessively out of the blood vessels and into the interstitial andalveolar spaces. The pressure gradient between the initial lymphaticsand at the outflow of the thoracic duct and the lymphatic duct isreduced and the lymphatic system cannot clear the additional fluid whichaccumulates in the air spaces of the lungs. This is a life threateningcondition as gas exchange is impaired to the extent that it may lead torespiratory failure.

Current treatments methods require extended hospitalization andtreatment with loop diuretics and or vasodilators. Oftentimes patientsmust also receive supplemental oxygen or, in more extreme cases, requiremechanical ventilation. Many of these treatment methods are less thanideal because the edema is not always alleviated rapidly enough and formany patients renal function is adversely affected. A significantpercentage of patients do not respond to this treatment and asignificant percentage must be readmitted to a hospital within 30 days.

A significant problem with current treatment protocol is that it isbased on the need to reduce intravascular blood pressure to movelymphatic fluid back into the vasculature. The reduction ofintravascular blood pressure leads to leads to hypotension and activatesthe Renin Angiotenesin Aldesterone System, which leads to an increase inblood pressure. Eventually, this cycle leads to diuretic resistance andthe worsening of renal function in almost 30% of admitted patients.

Accordingly, there remains a need for improved methods and devices forthe rapid and effective removal of excessive fluid that accumulates as aresult of pulmonary edema.

SUMMARY

Various methods and systems are provided for treating edema. In oneaspect, the method includes implanting an indwelling catheter within avein of a patient. The catheter can extend from a position upstream ofat least one outflow port of a duct of the lymph system to a terminalposition downstream of the at least one outflow port. A firstrestriction can be created within the vein proximal to a distal regionof the catheter. The first restriction can define a localized lowpressure zone distal of the restriction and within a portion of the veinhousing the catheter. The localized low pressure zone can be adjacent tothe at least one outflow port to enable fluid to pass from the at leastone lymph duct outflow port into the vein. The first restriction can bea selectively expandable balloon formed on an outer wall of thecatheter.

In another aspect, the method can include creating a second restrictionwithin the vein that is distal to the first restriction and adjacent adistal portion of the catheter. In this aspect, the localized lowpressure zone extends between the first and second restrictions. Thesecond restriction can be a selectively expandable balloon formed on anouter wall of the catheter.

In another aspect, the catheter used with the method of treating edemais a multilumen catheter that includes a suction lumen and a dischargelumen. The suction lumen can be in communication with a suction portformed in the catheter to withdraw fluid from the vein through theaction of an external pump. The discharge lumen can be in communicationwith a discharge line of the pump to return fluid to venous circulationthrough a discharge port in the catheter. In some aspects, the suctionport can be disposed between the first and second restrictions and thedischarge port can be disposed distal of the second restriction.

The catheter can be implanted in the internal jugular vein (right orleft) and advanced to a position such that the discharge port is distalto the junction of the subclavian vein (right or left, depending onwhether the catheter is implanted into the right of left internaljugular vein) and the internal jugular vein. The first restriction canbe within the internal jugular vein (right or left). The secondrestriction can be within the innominate vein (right or left), and thesuction port can be adjacent to the subclavian vein (right or left).

The catheter can include a plurality of control lumens, each configuredto receive a pressure sensor. The pressure can be monitored in at leastone position within the vein upstream of the first restriction, betweenthe first and second restrictions, and downstream of the secondrestriction.

In other aspects, a second catheter can be implanted within a secondvein. The second catheter can be in communication with an external pump.Fluid can be withdrawn from the second vein through the action of thepump and returned to the first catheter through a discharge line of thepump. In some aspects, the fluid can be discharged into the vein througha discharge port in the first catheter at a position downstream of thesecond restriction.

In some aspects, a hemofilter can be in communication with the dischargeline of the pump. A diverter can be upstream of the hemofilter to directsome amount of the fluid withdrawn from the patient back to venouscirculation while directing the remainder of the fluid to thehemofilter. After processing by the hemofilter, blood can be directedfrom the hemofilter back into venous circulation.

In another aspect, the system of treating edema, can include a cathetersystem configured for placement within a vein of a patient. The cathetersystem can have selectively deployable proximal and distal restrictionsdisposed within an indwelling portion of the catheter system. Thecatheter can include a blood inflow suction port disposed between theproximal and distal restrictions and in fluid communication with asuction lumen of the catheter system that is effective to remove fluidfrom venous circulation. A discharge port can be disposed distally ofthe distal restrictor and in fluid communication with a discharge lumenof the catheter and configured to return fluid to venous circulation.The system can include a pump configured to create a pressuredifferential to withdraw fluid from the suction port and through thesuction lumen to withdraw a fluid within a vein from venous circulationand to return the fluid to venous circulation through the dischargelumen and the discharge port. A plurality of pressure sensors can bedisposed within the catheter system. The pressure sensors can beconfigured to determine venous pressure upstream of the proximalrestriction, between the proximal and distal restriction, and downstreamof the distal restriction. The system also includes a control modulethat is to control operation of the system.

The pump can be configured to be positioned external to the patient, andin some aspects it can be a peristaltic flow pump.

In another aspect, an indwelling catheter configured to be implantablewithin a vein of a patient is provided. The catheter body can have aplurality of lumens, including a suction lumen configured to be incommunication with a suction port of a pump and a discharge lumenconfigured to be in communication with a discharge line of the pump. Thecatheter can further include a plurality of sensor lumens, eachconfigured to receive a pressure sensor, a selectively deployableproximal restriction disposed within a proximal region of the catheterbody and a selectively deployable distal restriction disposed on atleast a portion of an outer wall of the catheter body. The catheter caninclude a blood inflow suction port formed in a wall of the catheter andin fluid communication with the inflow lumen and a discharge portdisposed distally of the second restriction. The catheter can include aninflation lumen for each of the first restriction and the secondrestriction.

The distal restriction can be a selectively inflatable balloon. Inanother embodiment, the proximal restriction is a selectively inflatableballoon. In some embodiments, the distance between the proximal anddistal restrictions is in the range of about 1 to 15 cm. In someaspects, the suction port is disposed substantially midway between theproximal and distal restrictions.

In other embodiments, the indwelling catheter can have a diameter in therange of about 8 to 16 French. In some embodiments, each of the inflowlumen and the outflow lumen can have a diameter in the range of about 1to 4 mm.

A sensor port can be in communication with each of the sensor lumens. Insome aspects, a first sensor port can be disposed proximally of theproximal restriction, a second sensor port can be disposed between theproximal and distal restrictions, and a third sensor port can bedisposed distally of the distal restriction.

In another aspect, a method of positioning an indwelling catheter fortreating pulmonary edema is provided. The method includes inserting theindwelling catheter into a vein, such as the jugular vein of a patient.The indwelling catheter can be advanced until a distal restriction, aproximal sensor and a distal sensor positioned on the indwellingcatheter are disposed within the jugular vein of the patient. The distalrestriction can be activated until an initial pressure gradient ispresent between the proximal sensor and the distal sensor, which isdisposed distally of the distal restriction. The distal restrictoractivation level can be maintained at the activation level at which thepressure gradient is detected. The indwelling catheter can be advanceduntil the pressure gradient deviates from the initial pressure gradientbetween the proximal sensor and the distal sensor, thereby indicating adistal end of the indwelling catheter is positioned within a subclavianvein ostium of the patient. A percutaneous insertion length of theindwelling catheter can be observed. The indwelling catheter can then beadvanced a pre-determined distance until the distal restrictor is withinan innominate vein of the patient.

In yet another aspect, a system for treating edema includes a stentconfigured for placement within a vein of a patient. The stent hasopposed ends with an expanded diameter configured to engage walls of avein and a central portion having a reduced diameter. The stent furtherincludes a fluid conduit extending therethrough from a first end to asecond end and a suction conduit extending from a suction port formed ina central portion of the stent. The system also includes a pumpconfigured to create a pressure differential to withdraw fluid from thesuction port and through the suction conduit to withdraw a fluidadjacent to the suction port and the discharge port. A control module isalso included in the system to control operation of the system.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more fully understood from the following detaileddescription taken in conjunction with the accompanying drawings, inwhich:

FIG. 1 is a schematic view of a system to treat pulmonary edema havingan indwelling catheter and a pump;

FIG. 2 a perspective view of an embodiment of an indwelling catheter;

FIG. 3 is a detailed perspective view of a portion of the indwellingcatheter as shown in FIG. 2;

FIG. 4 is a perspective view of a distal portion of an alternateembodiment of an indwelling catheter;

FIG. 5 is a cross sectional view of the indwelling catheter of FIG. 4 atline 5-5;

FIG. 6 is a cross sectional view of the indwelling catheter of FIG. 2 atline 6-6;

FIG. 7A is a side perspective view of a portion of an indwellingcatheter of the type shown in FIG. 2 having a restriction in a deflatedconfiguration;

FIG. 7B is a side perspective view of a portion of an indwellingcatheter of the type shown in FIG. 7A having a restriction in aninflated configuration;

FIG. 7C is a side perspective view of a portion of another embodiment ofan indwelling catheter having an alternate restriction in a deflatedconfiguration;

FIG. 7D is a side perspective view of a portion of another embodiment ofan indwelling catheter of the type shown in FIG. 7C having an alternaterestriction in an expanded configuration;

FIG. 7E is a cross sectional view at line 7E-7E of the indwellingcatheter shown in FIG. 7C with the restriction in a deflatedconfiguration;

FIG. 7F is a cross sectional view at line 7F-7F of the indwellingcatheter shown in FIG. 7D with the restriction in an expandedconfiguration;

FIG. 7G is a side perspective view of a portion of an indwellingcatheter having a retaining frame and a restriction in a deflatedconfiguration;

FIG. 7H is a side perspective view of a portion of the indwellingcatheter as shown in FIG. 7G having the restriction in an inflatedconfiguration;

FIG. 8 is a schematic view of an alternate embodiment of an indwellingcatheter and frame in a deployed configuration;

FIG. 8A is a further schematic view of the indwelling catheter and frameof FIG. 8 in a deployed configuration;

FIG. 9A is a schematic view of an alternate embodiment of a system totreat pulmonary edema including a hemofilter and a diverter;

FIG. 9B is a schematic view of an alternate embodiment of a system totreat pulmonary edema including a hemofilter;

FIG. 10 is a block diagram schematically illustrating operation of acontrol module for a system for treating edema;

FIG. 11A is a flow diagram for operation of a control module for asystem for treating edema;

FIG. 11B is a flow diagram for an alternative technique for placing acatheter within a patient according to a method of treating edema;

FIGS. 12-15 schematically illustrate an indwelling catheter beingimplanted within the venous system of a patient according to a method oftreating edema;

FIG. 14 is a graphical representation of the pressure gradient measuredby the catheter as the catheter is advanced within a patient,approximately to a position shown in FIG. 11;

FIGS. 15-16 schematically illustrate and indwelling catheter beingimplanted within the venous system of a patient according to analternate method of treading edema;

FIG. 17 is a graphical representation of the pressure gradient measuredby the catheter as the catheter is withdrawn within a patient,approximately to a position shown in FIG. 13;

FIG. 18 is a schematic view of an alternate activation techniqueincluding electrical stimulation;

FIG. 19 is a schematic view of an alternate pressure gradient creationmethod including a plurality of restrictor stents positioned proximateto a lymphatic duct;

FIG. 20 is a schematic view of an alternate method of fluid pathcreation depicting a kink resistant stent placed within a thoracic ductof a patient;

FIG. 21 is a schematic view of a single lumen catheter having two oneway valves inserted within a patient;

FIG. 22 is a schematic view of the catheter as shown in FIG. 20 furtherdepicting fluid flow from the distal end of the catheter;

FIG. 23 is a side perspective view of an alternate catheter embodimenthaving a propeller;

FIG. 24 is a side perspective view of an alternate catheter embodimenthaving a piston;

FIG. 25 is a schematic view of an alternate catheter embodiment having asplit catheter configuration;

FIG. 26 is a schematic view of an alternate catheter embodiment having aconfiguration with dual tapered ends;

FIG. 27 is a schematic view of an alternative embodiment in which thecatheter is positioned in both the jugular vein and the superior venacava;

FIG. 28 is a schematic view of an alternate catheter embodiment having aconfiguration with dual tapered ends positioned in both the jugular veinand the superior vena cava;

FIG. 29 is a schematic view of an alternate catheter embodiment havingthree tapered sections; and

FIG. 30 is a schematic view of an alternate catheter embodiment havingan hourglass configuration.

DETAILED DESCRIPTION

Certain exemplary embodiments will now be described to provide anoverall understanding of the principles of the structure, function,manufacture, and use of the devices and methods disclosed herein. One ormore examples of these embodiments are illustrated in the accompanyingdrawings. Those skilled in the art will understand that the devices andmethods specifically described herein and illustrated in theaccompanying drawings are non-limiting exemplary embodiments and thatthe scope of the present invention is defined solely by the claims. Thefeatures illustrated or described in connection with one exemplaryembodiment may be combined with the features of other embodiments. Suchmodifications and variations are intended to be included within thescope of the present invention.

Reference throughout the specification to “various embodiments,” “someembodiments,” “one embodiment,” or “an embodiment,” or the like, meansthat a particular feature, structure, or characteristic described inconnection with the embodiment is included in at least one embodiment.Thus, appearances of the phrases “in various embodiments,” “in someembodiments,” “in one embodiment,” or “in an embodiment,” or the like,in places throughout the specification are not necessarily all referringto the same embodiment. Furthermore, the particular features,structures, or characteristics may be combined in any suitable manner inone or more embodiments. Thus, the particular features, structures, orcharacteristics illustrated or described in connection with oneembodiment may be combined, in whole or in part, with the featuresstructures, or characteristics of one or more other embodiments withoutlimitation.

It will be appreciated that the terms “proximal” and “distal” may beused throughout the specification with reference to a clinicianmanipulating one end of an instrument used to treat a patient. The term“proximal” refers to the portion of the instrument closest to theclinician and the term “distal” refers to the portion located furthestfrom the clinician. It will be further appreciated that for concisenessand clarity, spatial terms such as “vertical,” “horizontal,” “up,” and“down” may be used herein with respect to the illustrated embodiments.However, surgical instruments may be used in many orientations andpositions, and these terms are not intended to be limiting and absolute.

In general, methods and devices are provided for reducing edemaconditions, such as pulmonary edema, in a patient by lowering theoutflow pressure in a region around the thoracic/lymphatic duct outflow.As a result of lowering the outflow pressure at the thoracic and/orlymphatic ducts, higher lymphatic return will be achieved, enabling thelymphatic vessel flow to be at or near normal levels. In an exemplaryembodiment, the systems and methods are particularly useful to treatacute pulmonary edema, however a person skilled in the art willappreciate that the systems and methods can be used in variousprocedures for treating a lymphatic system fluid clearance imbalance. Inone embodiment, a catheter is provided for implantation within the veinof a patient in the vicinity of an outflow port of a duct of thelymphatic system. A first restriction can be created within the veinadjacent to a proximal region of the catheter and second restriction canbe created within the vein adjacent to a distal region of the catheter.The first and the second restrictions define a localized low pressurezone within a portion of the vein housing the catheter. The low pressurezone can be adjacent to an outflow port to enable fluid to pass from thelymph duct outflow port to the vein.

A person skilled in the art will appreciate that the surgical systems,methods and devices disclosed herein can be used with a variety ofsurgical devices, including measuring devices, sensing devices, locatordevices and insertion devices, etc.

The embodiments described herein generally relate to systems and methodsfor treating edema, including pulmonary edema. In some embodiments, thesystem can include any one or more of the following components: anindwelling catheter, a plurality of sensors, a control module, and apump. The components of the system can rapidly alleviate the edema andincrease the patient response rate.

FIG. 1 schematically illustrates one embodiment of a system 10 fortreating pulmonary edema that includes an indwelling catheter 20implanted within a vein of a patient and a pump 50, external to thepatient, that is coupled to the catheter via drainage tubing 40. Thepump and catheter system are positioned and cooperate so as to restrictblood flow within a vein, such as the jugular vein, so that the pressurein a localized region at the junction of the lymphatic vessel with thesubclavian or jugular vein can be reduced. The indwelling catheter canhave a proximal end 20 p coupled to drainage tubing 40 that is incommunication with the pump and a distal end 20 d. As explained indetail below, the catheter 20 can be a multilumen catheter, withseparate lumens to withdraw fluid from the vein to the pump 50 and toreturn fluid from the pump to the vein. Moreover, the catheter 20 canhave a suction port 26 for withdrawing fluid from the vein into asuction lumen of the catheter for transport to the pump, and a dischargeport 38, which can be at the distal end 20 d of the catheter for thedischarge of fluid back to the vein. The catheter 20 can also includepressure sensors and one or more selectively deployable restrictions(such as a first restriction 22, a second restriction 24) and thecontrol lumens that communicate with the pressure sensors andrestrictions.

The deployment of one or more of the restrictions, in combination withthe rate at which fluid is removed from the vein, enables a pressuredifferential to be created in a localized region downstream of the firstrestriction 22 and adjacent to the junction of the jugular andsubclavian veins, which is in the vicinity of the outflow ducts of thethoracic and/or lymphatic ducts. The pump 50 can be configured to removefluid from the suction lumen of the catheter 20 (and thus the vein)through the pump and back through the catheter toward the distal end 20d for discharge back into the venous system at an appropriate rate toachieve the desired pressure differential. A control module configured,also discussed below, can be used to control the operation of thesystem.

Although, the system can be implanted with both proximal and distalrestrictions, it can also be implanted with a single restriction asdiscussed below.

The systems and methods described herein have a number of advantagesover existing techniques for treating pulmonary edema. In particular, ahigher rate of fluid return from the thoracic and lymphatic outflowducts enables faster lymphatic fluid removal and resolution of the edemaepisode. A risk of developing acute heart failure or compromised renalfunction may be avoided by rapid lymphatic fluid removal from thelymphatic system. As a result of this treatment method pressure in arelatively large area surrounding the thoracic and lymphatic ductsoutflow ducts can be reduced thereby allow the procedure to be performedwithout complicated navigational guidance.

A person skilled in the art will appreciate that a variety of indwellingcatheter systems can be used to create the localized low pressure regiondescribed herein. FIGS. 2-4 illustrate an exemplary indwelling catheter20 that can be used with the system described herein. The catheter 20 isconfigured such that at least a portion thereof is to be implantedwithin a vein of the patient, such as the internal jugular vein. Asexplained below, the catheter 20 is positioned such that a proximalportion that is implanted within the jugular vein is at a position thatis upstream or proximal to the junction of the subclavian vein and adistal portion 20 d is downstream or distal to this junction and mayextend into the innominate vein.

It is understood that a variety of indwelling catheters can be used withthe systems and methods described herein. By way of example, indwellingcatheter 20 is a multilumen catheter having a generally elongate tubularshape, with a circular or ovular cross-sectional geometry as is known tothose skilled in the art. The indwelling catheter 20 can includeproximal end 20 p, which is configured to be placed outside of apatient's body, and distal end 20 d, which is configured for placementwithin a patient's vein.

In one embodiment, the indwelling catheter 20 can include at least twolumens, including one to accommodate the flow of fluid from the vein inwhich the catheter is implanted to the pump 50, and one to accommodatethe return of fluid from the pump to the vein. As shown in FIGS. 3 and5, the catheter has a first lumen 34 and a second lumen 36 in aside-by-side relationship, both of which accommodate fluid flow betweenthe vein and the pump 50. The first lumen 34 can be a suction lumen thatextends from a suction port 26, formed in an outer wall 20 o of catheter20, to the proximal end of the catheter 20 p. The proximal end 20 p ofthe catheter 20 can include a hub 30 which communicates with dischargetubing 40 coupled to the pump 50 as shown in FIG. 1. Fluid is withdrawnfrom the vein through the suction port and into first (suction) lumen 34so that it can be communicated to pump 50 via the discharge tubing 40.The second lumen 36 can be a discharge lumen that extends from theproximal end 20 p of the catheter to discharge port 38 at the distal end20 d of the catheter 20. The discharge lumen 36 communicates via the hub30 with the discharge tubing 40 of the pump 50 to return fluid from thepump 50 to venous circulation. To facilitate discharge and minimizeretrograde backflow into the low pressure area the indwelling cathetercan include a flared discharge port 38, as shown in FIG. 1. Although thefirst and second lumens 34, 36 are illustrated to be oriented in aside-by-side relationship with respect to one another, they can beoriented in any other suitable manner, including having one lumendisposed within the other lumen. As also discussed below, the catheter20 can have a number of additional lumens, which function as controllumens to facilitate activation of restrictions within the catheterand/or to sense pressure at various locations within the vein in whichthe catheter is disposed.

As mentioned above and further shown in FIG. 2, the hub includes suctionand discharge ports 42, 44, which can include surface features formedthereon and extending therearound to facilitate connection to dischargetubing 40. The inflow and outflow ports 42, 44 are configured to connectto drainage tubing having a first and a second end that is configured tobe in fluid communication with the pump. The pump can facilitate fluidmovement from the suction lumen through the outflow port 44 and into thedischarge tubing through which it is communicated to the pump. The fluidcan continue from the pump and into the drainage tubing through which itis communicated to the inflow port 42 and the discharge lumen within theindwelling catheter. Fluid is returned fluid back into venouscirculation through the discharge lumen 36 so that it can be dischargedat the distal end 20 d of the indwelling catheter 20.

As shown in FIG. 2, the hub 30 also includes a number of ports 32 a, 32b, 32 c, 32 d and 32 e in fluid communication with control lumens withinthe catheter. As shown in FIGS. 2, 3, and 6, port 32 d communicates withlumen 48 p, which is configured to deliver fluid to restriction 22 tocontrol the activation and deactivation of restriction 22. Similarly,port 32 a communicates with lumen 48 d, which is configured to deliverfluid to restriction 24 to control the activation and deactivation ofrestriction 24. Ports 32 b, 32 e, and 32 c communicate, respectively,with control lumens 46 p, 46 m, and 46 d. Control lumens 46 p, 46 m, and46 d, for example, can include pressure sensors to be used for sensingpressure at various locations along the vein in which the catheter isimplanted. As shown in FIGS. 2-3 and 6, port 32 b communicates withlumen 46 p, which communicates with opening 28 p in catheter 20 forpurposes of sensing a pressure within the vessel in the vicinity ofopening 28 p, i.e., at a location proximal to restriction 22. Similarly,port 32 e communicates with lumen 46 m, which communicates with opening28 m in catheter 20 for purposes of sensing a pressure within the vesselin the vicinity of opening 28 m, i.e., at a location distal torestriction 22 and in proximity to suction port 26. Also, port 32 ccommunicates with lumen 46 d, which communicates with opening 28 d incatheter 20 for purposes of sensing a pressure within the vessel in thevicinity of opening 28 d, i.e., at a location distal to restriction 24.

A person skilled in the art will appreciate that a variety of suitablesensors can be used for monitoring pressure.

As shown in FIG. 6, the catheter can be configured with the suctionlumen 34 and the discharge lumen 36 oriented in a side-by-sidearrangement. The control lumens 46 p, 46 m, 46 d, 48 p, and 48 d can bedisposed in the wall of the catheter 20. As indicated above, the crosssectional arrangement can have various embodiments. It is understoodthat the relative positioning of lumens 34 and 36 and control lumens 46p, 46 m, 46 d, 48 p, and 48 d can vary. A person skilled in the art willalso appreciate that more or fewer lumens and control lumens can beprovided in the catheter 20. For example, the control lumens canaccommodate a variety of other sensors, such as heart rate sensors orbreathing sensors which can be configured to be activation sensors.

A person skilled in the art will appreciate that the size of thecatheter 20 can vary depending upon its intended uses. Generally, thecatheter has a length in the range of about 15 to 50 cm. In addition,the diameter can also vary, but suitable catheters will typically be inthe range of about 8 to 18 French. Similarly, the diameter of lumens 34and 36 and control lumens 46 p, 46 m, 46 d, 48 p, and 48 d can varydepending upon the requirements of a given application. Lumens 34 and 36can have a diameter in the range of about 1 to 4 mm while control lumens46 p, 46 m, 46 d, 48 p, and 48 d can have a diameter in the range ofabout 0.1 to 0.5 mm.

As noted above, the indwelling catheter 20 includes at least onerestriction to at least partially occlude the vein within which it isimplanted and thus to restrict fluid flow within the vein when it isactivated. A first restriction 22 is shown in FIGS. 2-5 as beingpositioned at a portion of the implanted catheter that is proximal todistal portion 20 d. Typically, the first restriction 22 is positionedat a region of the catheter 20 that is proximal to suction port 26 andthat will mark the proximal or upstream boundary of the reduced pressureregion. By way of example, in a catheter implanted within the jugularvein, as shown in FIG. 1, the first restriction is proximal to (upstreamof) the point at which the subclavian vein enters the jugular vein. Theindwelling catheter can optionally include a second restriction 24positioned distally of the first restriction 22 and between the suctionport 26 and the distal end 20 d of the catheter 20. By way of example,and as shown in FIGS. 1-3, in a catheter implanted within the jugularvein, the second restriction 24 is distal to the point at which thesubclavian vein enters the jugular vein, and it can be in the innominatevein.

Although the system can be used with proximal and distal restrictions,it can also be implemented with a single proximal restriction.

A person skilled in the art will appreciate that the restrictions cantake a variety of forms as long as they are effective to at leastpartially occlude the vessel within which they are deployed. Theproximal restriction 22 should be configured so as to partially restrictflow when it is activated, but to allow some fluid to flow past therestriction. The distal restriction 24, on the other hand, can beconfigured to fully restrict fluid flow when it is activated. Thepurpose of the restrictors is to allow the normal flow of blood tocontinue. However, the activation of the restrictions creates alocalized pressure differential between the region proximal to theproximal restriction and the region between the two restrictions.

In some embodiments, as shown in FIGS. 2 and 3, the first and secondrestrictions 22, 24 can be in the form of a symmetrical inflatablemember, such as a balloon, that will expand in a uniform manner around acenter axis of each restriction. The proximal restriction can beconfigured and/or activated such that when fully activated or inflated,the restriction will not occupy the entire diameter of the vein withinwhich it is positioned. A person skilled in the art will appreciate thatthe restriction (e.g., a balloon) can be configured in a number of waysso as not to occupy the entire diameter of the vein in which it isdeployed. For example, and as described below, the restriction can beconfigured to expand asymmetrically, such as by having part of the outerwall of the restriction attached to the outer wall of the catheter sothat uniform expansion of the restriction is prevented. Typically, inthe expanded condition the first restriction 22 will occupy about 50 to90 percent of the diameter of the vein within which it is implanted. Thedistal restriction 24 can be similarly configured if it is to permitsome fluid flow and not fully occlude the vein. On the other hand, thedistal restriction 24 can be configured to fully occupy the diameter ofthe vein when it is activated.

FIG. 4 illustrates one example of a catheter 20′ that is similar inconstruction to catheter 20, described above, except that proximalrestriction 22′ is configured to expand asymmetrically to ensure onlypartial occlusion of the vein within which it is implanted. Catheter 20′includes a suction port 26 and a discharge port 28, which is adjacent todistal portion 20 d. Restriction 22′ is disposed proximal to suctionport 26 and, as noted above, it is configured to expand asymmetricallywhile distal restriction 24 expands symmetrically. As shown in FIGS. 4and 5, restriction 22′ can be of a non-circular shape in its expandedcondition such that it does not circumscribe the entire circumference ofcatheter 20′. In one example, restriction 22′ can be substantiallykidney-shaped with a body portion 23 that serves to occlude the vein inwhich it is implanted and a gap in the body portion that is positionedbetween body edges 23 a, 23 b. The restriction 22′ can be configured toocclude approximately 50 to 95 percent of the diameter of the vesselwithin which it is positioned. A person skilled in the art willappreciate that restriction 22′ can be assembled to the catheter in anumber of ways to enable the formation of a kidney-like shape uponexpansion that serves to partially occlude a vessel. For example, FIG. 5shows that the catheter 20′ can have the restriction 22′ extending fromonly a portion of the circumference of the catheter 20′, for examplefrom only about half of the catheter. The catheter can further include adistal tip 28 d′ that includes a discharge port that can facilitatefluid transport from the catheter back into the venous system.

A person skilled in the art will appreciate that the restrictions 22,22′, and 24 can be in the form of a balloon of the type typically usedin interventional medical devices, such as a compliant or semi-compliantballoon. Accordingly, the restrictions can be made of a variety ofmaterials that expand upon the delivery of a fluid thereto and contractupon the withdrawal of such fluid. Exemplary materials from which therestrictions can be made include polymeric materials such as PEBAX,silicones, polyurethanes, and nylons.

As noted above, the restrictions can be activated and deactivated duringthe treatment procedure. For example, FIGS. 7A and 7B illustrate arestriction 122 in the form of a balloon or a double balloon. Therestriction 122 can be formed around all or a part of the outer wall ofthe catheter, and it can be in fluid communication with a control lumensuch as an inflation lumen. When a fluid is communicated to therestriction 122 to effect inflation, the control lumen can remain at theinitial fixed diameter while the restriction expands. FIG. 7Aillustrates the restriction 122 in an inactivated or deflated state inwhich it is contracted and surrounding an outer wall of the catheter120. FIG. 7B illustrates the inflation lumen 124 and restriction 122 inan expanded or inflated form.

In some embodiments, alternate geometries can be used for therestrictions to prevent the restriction from fully occluding a vein orto prevent the vein lumen from fully collapsing on the indwellingcatheter. For example, FIGS. 7C-7F illustrate another embodiment of arestriction positioned on an indwelling catheter 140. FIG. 7Cillustrates an alternate restriction 142 in an inactivated or deflatedstate and FIG. 7E is a cross sectional view of the catheter 140 of FIG.7C. As shown, the restriction 142 can be in the form of three balloonsegments 146 a, 146 b, 146 c that can be positioned around the outercircumference of the catheter 140 and that are separated by threerestriction nodes 144 a, 144 b, 144 c that constrict the balloonsegments 146 a, 146 b, and 146 c. FIG. 7D is a perspective view of theindwelling catheter 140 in an expanded position, while FIG. 7Fillustrates a cross sectional view of the indwelling catheter 140 withthe three restriction nodes 144 a, 144 b, 144 c constricting the balloonsegments 146 a, 146 b, and 146 c when the balloon segments are inexpanded state. The restriction nodes 144 a, 144 b, 144 c can be fullyor partially engaged and can be expanded uniformly or to varyingpositions based on the particular constraints of the anatomy of thepatient. The constraints positioned around the circumference of therestriction can prevent the restriction from expanding in a circulargeometry. Restriction of the circular geometry can ensure that blood canflow past the restriction at all times and is a safety mechanism againstthe vein collapsing on the restriction and restricting blood fromflowing past the first or the second restriction. A person skilled inthe art will appreciate that the formation of balloon segments can beachieved by the use of an external restrictive structure, such as rigidcup with three openings which is mounted external to the balloon.Alternatively, the balloon segments can be formed by bonding the ballooninner wall to the catheter shaft along three longitudinal lines.Alternatively, the balloon can be bonded to the shaft alongcircumferential segment. Such a segment will not be free to inflate andthus only the free, non-bonded segment will be inflated, resulting in anasymmetric cross section of the balloon.

In some embodiments, as shown in FIGS. 7G-7H, a covered frame or anactivation wire comprising a braided wire or the like can be used toconstrict or modify the geometry of the restrictions. For example, FIG.7G illustrates a perspective view of an indwelling catheter 160 with arestriction 162 in an initial or an unexpanded state. The restriction162 is surrounded by a braided wire 164. Upon activation, as shown inFIG. 7H, the restriction 162 can expand but, the covered frame 164limits the expansion to prevent the restriction 162 from expanding intoa full circular geometry.

Other restriction designs are possible as well. In some embodiments, aframe can be used to isolate the area proximate to the outflow duct. Asshown in FIG. 8, this embodiment can utilize a catheter 820 coupled to aNitinol frame 816. The catheter can be configured to a L-shape uponactivation of the Nitinol frame, with a guiding distal end 820 d, arounded midsection 820 m having a suction port 826, and a proximalsection 820 p having a discharge port. The catheter 820 can be proximateto or coupled directly to the frame. The frame 816 can be formed of ashape memory material that can be crimped during insertion to about 14Fr or less and can be introduced to the bifurcation of the jugular vein.The crimped section of the frame can expand from an initial positionwrapped or closely aligned with the catheter to a u-shaped geometry asshown in FIG. 8, upon deployment within the left or right sides of thesubclavian 402 or internal jugular veins 400. The frame 816 can includea membrane 818, stretched across the frame to partition a low pressurezone proximate to the thoracic duct. As shown in FIG. 8A, the frame canhave an additional segment 819 that will support either the innominatevein 821 wall or both the innominate vein wall and the subclavian veinwall 823 to ensure contact of the membrane edge with the venous wall toenable pressure reduction of the isolated area. Also, the frame segmentswithin the subclavian and jugular vessel can have multiple struts 825that will ensure a patent section for blood flow. The membrane can beformed from polymeric materials such as polyurethane, silicones,polyethylene terephthalate (PET), and polyethylene tetrafluoroethylene(PTFE). Additionally, materials having varying levels of porosity canalso be used. Exemplary materials with varying levels of porosityinclude expandable polyethylene tetrafluoroethylene (ePTFE), PET fabric,and polyester fabric.

The catheter can be inserted into a vein such as the jugular vein (oneither the right or left side of the patient's body) and advanced to aposition in the vicinity of a bifurcation in the vein and advanced toposition the portion of the frame having the membrane proximate to thethoracic duct. After insertion of the catheter, the frame can bedeployed from the crimped position to the expanded position, forming anangled configuration segmenting a portion of the vein from thesurrounding area. Thereafter, the area proximate to the thoracic duct isisolated and fluid can be removed via a suction port positioned on thecatheter located within the isolated area. Fluid can then be dischargedthrough the discharge port on the catheter back into the venous systemwithin the jugular vein 400. As explained below, the pumping of fluidcan be performed by a rotating impeller within the catheter between thesuction and discharge ports, or by an external pump such as peristalticpump that will pump the fluid from the isolated area through suctionlumen outside the patient and then return the fluid through thedischarge lumen to the blood stream outside of the isolated area. Apressure sensing lumen, which is positioned proximately to the cathetersuction port within the isolated area, can be used to control the rateof suction by maintaining the pressure of the isolated area betweenabout 2-5 mmHg and thus prevent collapse of the thoracic duct due toexcessive suction and ensure optimized lymph drainage. The patent areabehind the membrane enables blood flow from the subclavian and jugularvein without interruption.

For all active platforms for regulating lymphatic flow including pumps,mechanical activation, electrical activation and neural activation thesystem may include sensors that may help optimize the lymphaticregulation. In addition to the placement of such sensors in theindwelling catheter, the sensors can be placed at various positions thatmay be prone to the accumulation of interstitial fluid. For example,blood pressure sensors can be placed in the venous system, in the heart,in the arterial system, at the junction of the subclavian and jugularveins, and in the body at other target sites. Additionally, another typeof sensor, such as a fluid sensor, can be used to measure the amount offluid in the body, specifically in the interstitial spaces of the lungs.The sensors can detect a rise in the fluid or the pressure of the lungcavity and actuate the pump to enable higher flow volumes to enhance thelymphatic clearance. Such sensors may further include bioimpedancesensors, radio frequency transmitters and receivers, and optical meansthat measure changes in the body organ dimensions. Additional sensorsmay include heart rate sensors, breathing sensors and activity sensors.

In the event that a patient develops edema, an acute treatment optioninvolves implanting within the patient's venous system, such as theinternal jugular vein, an indwelling catheter of the type discussedabove. The catheter can be coupled through fluid return tubing via anexternal pump 50 to connect the suction lumen of the catheter to thedischarge lumen via drainage tubing. The pump 50 can be operated tocreate a localized low pressure region at the junction of the jugular,subclavian and innominate veins to establish a pressure gradient in thevicinity of the thoracic and lymphatic duct outflow.

A person skilled in the art will appreciate that a variety of pumps canbe used as part of the system 10 described herein. Examples of suitablepumps include peristaltic pumps, impeller pumps, and piston pumps. Insome embodiments, a peristaltic pump can be used to withdraw fluidthrough the indwelling catheter to reduce pressures surrounding thethoracic and lymphatic duct outflow thereby assisting in removing excesslymphatic fluid from the thoracic and/or the lymphatic duct. Suitablepumps, for example, should be capable of operating at a flow rate in therange of about 100 ml/min to 800 ml/min and typically in the range ofabout 400 ml/min to 800 ml/min. Pump operation in the range of about 400ml/min to 800 ml/min can reduce the pressure in the vicinity of thethoracic and lymphatic duct outflow by more than about 50%. For example,the optimal outflow pressure of the thoracic and lymphatic duct outflowis approximately 5 mmHg, and pressures in excess of 25 mmHg cancompletely stop lymphatic return. The pump can be operated to reducehigh pressures at the thoracic and lymphatic duct outflow to anoptimally low pressure in the range of about 2 mmHg to 6 mmHg in—lessthan about twenty-four hours. Exemplary pumps include the Watson Marlow520R2 peristaltic pump head with 0.64 mm bore and 2.4 mm wall silicontubing pump.

The low pressure region corresponds to the drainage ports of thethoracic and lymphatic ducts and can enable enhanced clearance oflymphatic fluids. For example, the pressure between the firstrestriction and the second restriction will be reduced often from about10 mmHg-20 mmHg to about 2 mmHg-6 mmHg. The pressure at the distal endof the catheter proximate to the discharge port can be mildly elevatedbut by no more than 2 mmHg.

In some embodiments, ultrafiltration can be used to reduce acutelydecompensated heart failure via removal of fluids outside of the body.Ultrafiltration process, which can utilize a hemofilter as describedbelow, can be useful to remove additional fluid volume that was added tothe blood through the lymphatic system so as to not rely solely on thekidneys to remove excess fluid. As shown in FIG. 9A a hemofilter circuit700 can be incorporated into the system 10. After fluid exits pump 50through discharge tubing 40, it passes through a diverter 710. Diverter710 diverts a certain volume of fluid, generally equal to the amount oflymphatic fluid drained from the body (e.g., up to about 10 ml/min) anddiverts it to hemofilter through line 712. The remaining volume of fluidis allowed to flow into a downstream section of discharge tubing 40through line 714. Such a diverter can be in the form of “Y” connector.As the accumulated pressure drop along lines 712, 714, and 718 (filterline) equals the pressure drop along 714 line, proper selection of theinner diameter and length of line 714 can help achieve the desired bloodflow rate through the hemofilter 716. In one example, a filter issuitable to work with blood flow rate of about 100-500 ml/min, where thetotal blood flow through the system is about 600 ml/min. At a blood flowrate of about 200 cc/min the filter can be expected to have a pressuredrop of about 30 mmHg. In this example, the line 714 segment is 25 cm inlength with 2.5 mm inner diameter. At a blood flow of 400 cc/min throughline 714, the pressure drop is 30 mmHg and thus matches the pressuredrop along the filter line. As shown in FIG. 9A, line 712 passes theexcess fluid to a hemofilter 716 where the blood is separated from thelymphatic fluid. Blood is passed from hemofilter 716 back intodownstream discharge tubing 40 through line 718. As shown in FIG. 9A,lymphatic fluid can be discharged from hemofilter 716 into a collectionchamber 720. A roller pump 722 may be placed in discharge line 724 tocontinuously regulate the volume of withdrawn lymphatic fluid.Alternatively, a clamp or tap may be placed in the discharge line 724and regulation of withdrawn lymphatic fluid can be achieved be openingand closing the clamp or tap.

The use of a hemofilter can be advantageous to reduce the blood volumein the cardiovascular system, thereby reducing the pressure and allowingfluids to flow from the interstitial spaces back into the venous systemand relieve the edema. However, the reduced blood volume can adverselyimpact kidney function. The use of ultrafiltration as described hereincan reduce the pressure and fluid volume in a localized area where thelymphatic system drains into the venous circulation. The overall systemvolume is not reduced and thereby limits the adverse impact on thekidney function of a patient. In some embodiments, a controllable amountof the fluid is circulated through a pump and diverted to a filter.Typically it will be around 10 to 40 percent of the volume but it couldbe manipulated by a flow restrictor on a Y connector that diverts someof the flow into a filter. The filter can be configured to control theblood volume thereby preventing a change due to the lymphatic drainage.

In another embodiment, as shown in FIG. 9B, the hemofilter circuit 700can be incorporated into the system 10. After fluid exits pump 50through discharge tubing 40, it passes the excess fluid to thehemofilter 716 where the blood is separated from the lymphatic fluid.Blood is passed from hemofilter 716 back into downstream dischargetubing 40 through line 718. As shown in FIG. 8B, lymphatic fluid can bedischarged from hemofilter 716 into the collection chamber 720. A rollerpump 722 may be placed in discharge line 724 to control the volume ofwithdrawn lymphatic fluid.

A person skilled in the art will appreciate that a variety ofhemofilters can be used as part of the system 700 described herein.Suitable hemofilters, for example, should be capable of operating at aflow rate in the range of about 10 ml/min. Exemplary hemofilters includethe Sorin Hemocor HPH mini and the Sorin Hemocor HPH Junior.

The system to treat pulmonary edema can further include a control moduleto receive information from the sensors, activate the restrictions, andadjust the flow rate of the pump. In some embodiments, as shown in FIG.10, the system to treat pulmonary edema can include a control module 200configured to receive information from pressure transducers 209 a, 209b, 209 c including information regarding the pressure 208 within thejugular vein, the pressure 210 at the bifurcation of the jugular andsubclavian veins, and the pressure 212 at the innominate vein. Uponreceiving the data from the various pressure transducers the controlmodule can be configured to actuate the pump function of pump 203. Thecontrol module 200 can further be configured to process the datareceived from the various sensors to alter the first or secondrestriction volume 204, 206 via an automated, and travel controlledsyringe pump 205 a, 205 b.

The control module 200 can include multiple feedback loops to adjustperformance of the system 10 to create and maintain a low pressure zonewhile the lymphatic fluid is cleared. In some embodiments, as shown inFIG. 11A, A system to treat edema can include a control module 200configured to execute a process 300 to create a low pressure zone andtransport fluid from the low pressure zone back into the venous systemof a patient. For example, at step 302 the control module can acquirethe baseline measurement for the jugular pressure, the bifurcationpressure and the innominate pressure. The control module at step 304 canthen calculate the target bifurcation pressure to a value typically inthe range of about 3-5 mmHg. At step 306 the catheter can be placed andthe pump flow rate can equal zero, and the volume of the first and thesecond restrictions that can also be equal to zero. Next, at step 308the control module increases the pump flow rate. At step 310 the controlmodule determines if the baseline pressure is less than the baselinebifurcation pressure minus the pressure drop indicator. If this provesto be the case, the control process advances to step 312 and increasesthe volume of the second restriction. If the pressure baseline isgreater than the baseline bifurcation pressure minus the pressure dropindicator then the process returns to step 308 and the pump flow rate isthereby increased.

After the second restriction volume is increased, at step 314 the datafrom the jugular vein pressure is analyzed to determine if the jugularvein pressure is less than the baseline jugular pressure minus theminimum significant pressure deviation. If the jugular vein pressure isgreater than the baseline jugular pressure minus the minimum significantpressure deviation process continues to step 316. At step 316, analgorithm analyzes if the jugular pressure is greater than the baselinejugular pressure plus the safety delta. If yes, the process continues tostep 318, and the pump flow rate is less than the natural blood flowrate into the innominate vein. The process continues back to step 308and the pump flow rate is increased.

At step 316, if the jugular pressure is less than the baseline jugularpressure plus the safety delta then the process continues to step 310,where, as discussed above, step 310 determines if the bifurcationpressure is less than the baseline bifurcation pressure minus thepressure drop indicator. At step 310 the process either continues on tostep 312 or reverts back to step 308 as discussed above.

At step 314, if the jugular pressure is less than the baseline jugularpressure minus the minimum significant pressure deviation then theprocess continues on to process step 320, where the pump flow rate isgreater than the natural blood flow rate into the innominate vein. Theprocess then advances to step 322 where the first restriction inflationvolume is increased until the jugular pressure is greater than thebaseline jugular pressure. The process advances to step 324 where thecontrol module determines if the bifurcation pressure is greater thanthe target bifurcation pressure. The value of the target bifurcationpressure is typically in the range of about 3-5 mmHg. If the targetbifurcation pressure is greater than the baseline pressure then theprocess advances to step 328. If the bifurcation pressure is equal tothe target bifurcation pressure then the process stops at step 338. Insuch cases where the bifurcation pressure is unstable and exceeds thetarget bifurcation pressure, the process advances to step 336 to reducethe pump flow volume and the process returns to step 314 and repeats asdescribed above.

Alternatively, if at step 324, the bifurcation pressure is greater thanthe target bifurcation pressure then the process advances to step 326,where the second restriction inflation volume is increased. The processthen advances to step 300, where the algorithm determines if theinnominate pressure is greater than the baseline innominate pressureplus the safety delta. If yes, the process advances to step 332 wherethe pump flow rate is reduces and the process repeats step 330. If theinnominate pressure is greater than the baseline innominate pressureplus the safety delta, then the process reaches step 334 and reverts toprocess step 322 and advances as described above.

FIG. 11B illustrates an alternative technique for placing a catheterincluding process 350, which can be useful when there is preexistingknowledge of a patient's anatomy, for example as a result of dataprovided by fluoroscopy or another imaging technique that includes theinnominate vein diameter. According to this technique, the distalballoon is inflated to a known diameter, for example to about 10 percentgreater than the nominal innominate vein diameter. For example, at step352, the diameter of the innominate vein can be acquired by the controlmodule. The control module can measure baseline data for the jugularpressure, the bifurcation pressure and the innominate pressure at step354. At step 356, the target bifurcation pressure can be calculated bythe control module, typically, in the range of about 3-5 mmHg. At step358, the catheter can be placed. During placement of the catheter, thepump flow rate, the proximal balloon inflation volume and the distalballoon inflation volume are typically equal to about zero.

After the catheter is placed in the venous system, the pump flow ratecan be increased at step 360. After the pump flow rate is increased, atstep 362, the proximal balloon inflation volume can be increased tomatch the size of the innominate vein. In some embodiments, theinflation volume can be up to ten percent oversized. At step 364, thecontrol module applies an algorithm to analyze if the jugular pressureis less than the baseline jugular pressure. If not, at step 366, analgorithm is applied to confirm that the pump flow rate is less than thenormal blood flow rate into the innominate vein. The process thencontinues to step 360, where, as discussed above the pump flow rate canbe increased.

At step 364, if the jugular pressure is less than the baseline jugularpressure then, the process continues to step 368. At step 368, thecontrol module applies an algorithm to analyze whether the pump flowrate is greater than the natural blood flow rate into the innominatevein. Thereafter, at step 370, the proximal balloon inflation volume canbe increased until the jugular pressure is equal to the baseline jugularpressure plus a safety delta. The safety delta can typically be in therange of about 2-3 mmHg. At step 372, the control module applies analgorithm to measure the bifurcation pressure. If the bifurcationpressure is greater than the target bifurcation pressure, then theprocess can proceed to step 374, and the pump flow rate can beincreased. The process then can continue back to step 370 where, asdiscussed above, the proximal balloon inflation volume can be measured.

If at step 372, the bifurcation pressure is less than the targetbifurcation pressure, the process continues to step 376. At step 376,the control module applies an algorithm to confirm that the bifurcationpressure is less than the target bifurcation pressure. If yes, theprocess continues to step 378 where the pump flow rate can be decreasedand the process returns back to step 364. At step 364, the algorithm canmeasure jugular pressure and the process continues as described above.At step 376, if the algorithm confirms that the bifurcation pressure isequal to the target bifurcation pressure the process continues to step380 and the process terminates.

As mentioned above, an acute treatment for edema, as described herein,involves inserting an indwelling catheter into a vein of a patient. Insome embodiments, the method can include placing an indwelling catheterat an internal jugular vein (left or right) with a central lineprocedure, according to techniques well known to those skilled in theart. It is understood that the catheter can alternately be inserted intoopen veins such as the subclavian, external jugular or auxiliary veins.The placement technique is well known to those skilled in the art and itcan typically be conducted using a 12 Fr sheath to puncture the venouswall. The distal restriction, when activated, isolates the incomingblood flow from the subclavian and jugular veins from the blood flow ofthe innominate vein and ensures that all incoming blood is directed tothe pump. The pump is activated to maintain the jugular and innominatevein pressure and thus the nominal blood flow. The proximal restriction,when activated, creates a pressure gradient between the upper jugularvein and the subclavian vein. As the nominal pressure of the jugularvein is maintained by the actuation of the pump, the pressure gradientacross the proximal restriction is achieved by the pressure reductionwithin the area between the two restrictions. Actuation of the pumphelps to create a low pressure zone in the vicinity of the junction ofthe jugular vein and the subclavian vein by withdrawing fluid in thisregion, recirculating it through the pump, and discharging the fluiddownstream of this region. Because the outflow of the thoracic andlymphatic ducts is located in this region, the lower pressure willfacilitate drainage of lymphatic fluid.

FIGS. 12-14 illustrate methods for implanting an indwelling catheterwithin the vein of a patient. As shown in FIG. 10, the indwellingcatheter 20 can be inserted into the right internal jugular vein 400 ofa patient. The indwelling catheter 20 can then be advanced until thedistal restriction 24 and the distal pressure sensing opening 28 d, arewithin the jugular vein 400. The distal restriction 24 is activatedwhile the proximal pressure sensing opening 28 p and the distal pressuresensing opening 28 d measure the venous pressure both distal andproximal to the distal restriction 24. When a pressure gradient isachieved, typically about 2-5 mmHg, inflation of the distal restriction24 can be terminated. The indwelling catheter 20 can then be advancedfurther into the internal jugular vein 400, while the inflation of therestriction 24 is maintained and the pressure is monitored at theproximal pressure sensing opening 28 p and the distal pressure sensingopening 28 d. As shown in FIG. 14, when the proximal pressure sensinglumen and the distal pressure sensing lumen indicate a drop in thepressure gradient, the distal restriction has moved past the subclavianvein and into the subclavian vein ostium. The indwelling catheter 20 caninclude indicia that can be used to ascertain the distance that thecatheter has traveled within the vein of the patient. After the pressuredrop is detected, as shown in FIG. 13, the indwelling catheter 20 can beadvanced an additional 1-2 cm distally thereby moving the distalrestriction into the innominate vein 404.

In another embodiment, a catheter with a single restriction (e.g.,balloon) can be used. The catheter can also include two pressure sensingcontrol lumens, with one sensing pressure proximal to the restrictionand the other sensing pressure distal to the balloon. The catheter canbe used by positioning the restriction within the innominate vein and tofully inflate it to the vessel diameter. The flow rate applied to thepump will be greater than the natural rate of flow within the patient'svascular system. This higher flow rate of the pump will help to createlow pressure zone within the patient just proximal to the restriction.

In some embodiments, as shown in FIGS. 15-17, an alternate catheterinsertion technique can be used and catheter positioning can be achievedwithout the use of imaging modalities. As explained below, only thedistal restriction is utilized for purposes of catheter positioning andonly after the catheter is properly positioned is the system activated.By way of example, as shown in FIG. 15, the indwelling catheter isintroduced into the jugular vein 400 of the patient. The indwellingcatheter 20 is advanced approximately 15 cm thereby positioning thedistal end 20 d within the superior vena cava (SVC) 410 while the distalpressure sensing opening 28 d monitors the pressure. As shown in FIG.14, the distal restriction 24 is activated while the proximal pressuresensing opening 28 p and the distal pressure sensing opening 28 dmonitor the pressure. Once the pressure gradient is in the range ofabout 2-5 mmHg, the distal restriction 24 is maintained at its currentactivation level. After activation of the distal restriction 24,retrograde movement of the indwelling catheter 20 can begin while alsomonitoring the pressure gradient proximal to the distal restriction 24.As shown in FIG. 17, when the proximal pressure sensing opening 28 pindicates an elevated proximal pressure, the distal restriction 24 is ina position adjacent to the innominate vein ostium 408. As discussedabove, the catheter indicia can be used to indicate the insertiondistance and or position within a patient. The distal restriction 24 canthen be deactivated while moving the catheter retrograde by a distanceof about 1-2 mm, the distal restriction is now placed within theinnominate vein 404.

After positioning the indwelling catheter within the vein of a patientby a technique as discussed above, the indwelling catheter will have thesuction port 26 positioned proximate to an outflow port of a duct of thelymphatic system. The indwelling catheter's sensors can be used toattain a baseline pressure measurement in the internal jugular, SVC andthe junction of the jugular and subclavian veins. After establishing apressure baseline, the restrictions can be deployed and the pump can beactivated.

In some embodiments the pump can initially operate at a rate of about200 ml/min. In conjunction with the pump operation, the first and secondrestrictions 22, 24 can be activated and deactivated to adjust thepressure and thereby create a localized low pressure zone within aportion of the vein housing the indwelling catheter 20. The pump 50 cancontinue to increase the pump rate at increments of about 100 ml/minwhile the pressure is continuously monitored. The first and secondrestrictions 24, 26 can be adjusted to alter the innominate vein and theSVC pressures from the baseline. Once the localized low pressure zonehas been created, thereby reducing the pressure to about 50% itsbaseline value, or the pump has reached 800 ml/min, the systemparameters are held constant while the pump 50 continues to operate.

Alternate Catheter Embodiments

In some embodiments, alternate catheter designs can be used in place ofthe indwelling catheters discussed above. As discussed below, thesealternative catheters include, catheters with an alternate lumenconfigurations, catheters with a single lumen and a one way valve,catheters with a propeller operation, catheters having a pistonoperation, self-stabilizing catheters, and split action catheters.

In one embodiment, an alternate catheter can include a coaxial lumenconfiguration. For example, in an alternate lumen configuration an innerlumen can be positioned within an outer lumen. The outer lumen can haveperforations in the outer wall of the catheter that can be configured toact as the suction ports to extract fluid from the low pressure area.The inner lumen can be configured to be isolated from the outer lumenand can function as the discharge lumen. The coaxial lumen catheter canbe used in the system as described above to create a low pressure areaproximate to the lymphatic duct thereby removing fluid from the lowpressure area and returning the fluid to the venous system via theperistaltic pump.

In another alternate embodiment, as shown in FIGS. 21 and 22, a cathetercan have a single lumen 520 configured with two one-way valves, with onepositioned at the proximal restriction and one at the distal end of thecatheter. As shown in FIGS. 21 and 22, the pressure reduction viasuction and discharge can be performed in a pulsatile pattern. Forexample, when suction is performed in the single lumen catheter 520 afirst one way valve 524 will disable entry of blood from the dischargeport into the catheter. Fluid is drawn towards the proximal end of thecatheter thereby creating a low pressure area proximate to the lymphaticduct. Fluid can be drained from the lymphatic duct into the low pressurearea. Alternately, when discharge is performed fluid will move from theproximal end of the catheter toward the distal end. A second one wayvalve 522 will disable the discharge of fluids back into the suctionport and will ensure that the fluids are transported into the dischargeport 520 p and back into the venous system.

In another embodiment, a catheter can include a self-stabilizingmechanism. For example, in some embodiments catheters can be configuredto expand to a larger diameter once inserted within the vein of apatient. For example, a catheter can be inserted via a puncture siteinto the vein system having a diameter of about 6 Fr and expand to about15 Fr each immediately when inserted inside the vein. Such expansion ofa catheter can reduce the need for high velocity and turbulence of fluidflow. The only location where there will be a small diameter inside the12 Fr sheath that will assist in the crossing of the system through thevenous wall in the puncture site. The flaring and crimping of thecatheters can also be enabled upon retracting the system back throughthe sheath. The expansion and contraction of the system can eliminatethe need for a supplemental stability system as the embodiment canself-stabilize via its internal structural integrity.

In another embodiment, the catheter can include a propeller disposed inan inner lumen. As shown in FIG. 23, the propeller can be configured toadvance fluid from the proximal end of the catheter toward the distalend of the catheter, thereby advancing fluid within the vein of apatient. As discussed above, the catheter can be proximal to thelymphatic duct outflow to create a low pressure zone thereby creating apressure gradient to allow fluid flow from the lymphatic duct to passeasily into the low pressure zone. For example, the catheter 530 can beconfigured with a propeller 532 disposed in an inner lumen 534 such thatthe propeller is configured to rotate axially wherein fluid flowsbetween the first and second restrictions. The propeller canalternatively be actuated by an external force. As fluids flow into thecatheter 530 via the suction port 536 the propeller 532 can advance thefluid in a distal direction via the driving force of the propeller 532to transport the fluid from the distal end 530 d of the catheter intothe innominate vein of the patient. As the fluid is advanced within thevein the low pressure zone is maintained thereby allowing additionalfluid to pass from the lymphatic duct into the suction port.

As described above, with respect to the catheter configured with apropeller, some catheters can have a self-actuating mechanism to advancethe fluid within the catheter. In another embodiment, as shown in FIG.24, a catheter 540 can be configured with a piston 542 disposed in theinner lumen 544, a suction port that can be positioned toward themidsection of the catheter, a one way valve proximal to the suction portand a one way valve at a distal end of the catheter. The piston can bepositioned toward the proximal end of the catheter upstream of a suctionport. The piston can be configured to advance and retract axially fromthe proximal end of the catheter toward the distal end of the catheter.As discussed above, the catheter can be disposed within the vein of apatient proximal to a lymphatic duct. The retraction of the pistontoward the proximal end 540 p of the catheter 500 can create a suctionforce thereby allowing fluid into the catheter 540 via the suction port546. The piston 542 is then advanced forward toward the distal end 540 dof the catheter 500 and can drive fluid forward to discharge the fluidout the distal end 540 d of the catheter 500 into the vein of thepatient. Utilizing this embodiment requires a plurality of one-wayvalves at the suction port 546 and at the distal end 540 d of thecatheter to prevent fluid back flow.

In certain circumstances, a patient's condition or anatomy may not besuitable for treatment using a large venous catheter or an indwellingcatheter as described above. In some embodiments, a split actioncatheter method may be used to reduce the catheter crossing profile. Asshown in FIG. 25, a plurality of catheters may be used instead of asingle indwelling catheter. For example, a first catheter 600 caninclude a plurality of lumens including a fluid discharge lumen, aproximal pressure sensor lumen, a distal pressure sensor lumen, amid-point pressure sensor lumen, a first restriction, a secondrestriction, and an optional bifurcation pressure lumen. A secondcatheter 602 can include a fluid suction lumen and an optionalbifurcation pressure lumen. The first and the second catheters can beused in conjunction with one another to create a low pressure zone. Thefirst catheter 600 can be inserted into a patient through the internaljugular vein 400 and the second catheter 602 can be inserted into apatient via the subclavian vein 402. After positioning the catheters,the first and second restrictions 604, 606 of catheter 600 can beactivated on the first catheter 600 to create a localized low pressurezone proximate to the lymphatic duct. The low pressure zone canfacilitate fluid drainage from the lymphatic ducts into the low pressurezone. The fluid can be removed from the low pressure zone via the secondcatheter 602. As such, fluid can enter the proximal end of the secondcatheter and pass through the catheter toward its distal end. Outside ofthe body of the patient, the second catheter can be configured to thefirst catheter via drainage tubing or the like. The fluid can thentravel through the first catheter 600 entering into the proximal end 600p and be discharged via the distal end 600 d into the SVC. The pressuregradient can reduce the fluid in the lymphatic system thereby reducingthe edema.

ALTERNATE EMBODIMENTS

In some embodiments, an alternate activation technique such asmechanical compression can be used to regulate the lymphatic flow.Mechanical compressions can be applied using extra body elements or withimplantable elements that are preferably implanted in the torso. Forexample, mechanical compression elements can change their volumes ondemand and thereby enhance the lymphatic flow. In some embodiments, aballoon can be implanted in the thoracic cavity proximate to thealveoli. At elevated pressures, the balloon can inflate and thepressures around the entrance to the lymphatic vessels can be increased.The pressure gradient can facilitate fluid flow into the lymphaticsystem. In some embodiments, lymphatic flow can be regulated used muscleactivation. For example, the diaphragm muscle can be utilized to controlthe pressure in the torso and the lungs and can be synchronized topatient breathing patterns. Alternatively, the lymphatic muscles can becontracted to increase the rate and strength of contraction of theintrinsic or extrinsic pumps. The contraction pacing can enhance thenatural pumping actions thereby enhancing lymphatic return.

In other embodiments, an alternate activation technique such aselectrical simulation can be used to increase the lymphatic flow. Asshown in FIG. 18, a wire 502 with electrical stimulation electrodes canbe placed using catheterization in the thoracic duct and or thelymphatic duct vessels. The electrical stimulation can generateperistaltic action in the thoracic duct and/or the lymphatic ductvessels. In another embodiment, electrodes or an array of electrodes canbe placed in the trachea. The electrode can be proximate to thelymphatic vessels and will generate stimulation that can increase thelymphatic flow.

In another embodiment, shown in FIG. 26, a covered stent 800 with twotapered ends 800 d 1, 800 d 2 can be implanted in the jugular vein 400in proximity to the innominate vein 404. The large diameter ends 800 d1, 800 d 2 of the covered stent 800 are in contact with the entirevessel circumference. As shown, the thinner neck section 800 m of thestent 800 is positioned near the subclavian vein ostium 402 or thevenous angle. The entire flow of blood coming from the jugular vein 400is directed into the covered stent 800 and reaches the innominate vein404. The covered stent 800 has an opening 802 in the neck section 800 mthat is connected to a suction tube 810 that can be connected, forexample, to an extracorporeal pump 820, such as a peristaltic pump. Thisconfiguration enables the suction of blood from the subclavian vein andthe lymphatic duct and thus creates a low pressure zone between the twotapered ends 800 d 1, 800 d 2 of the stent 800. The blood can bereturned to the jugular vein 400 via a discharge tube 812. The volume ofblood that is circulated via the pump is lower because the natural bloodflow coming from the jugular vein is directed into the innominate veinand does not circulated through the pump.

In another embodiment, shown in FIG. 27, the catheter 20 can bepositioned such that the distal restriction 24 is positioned within thesuperior vena cava (SVC) 410 and the proximal restriction is within theright internal jugular vein 400. The positioning of the suction port(s)26 between the proximal and distal restrictions is such that blood canbe withdrawn from the right subclavian vein 402, and from the leftinnominate vein 403. This arrangement enables drainage of both the rightlymphatic duct and the thoracic duct.

In a further embodiment, shown in FIG. 28, a covered stent 900 withtapered end sections is inserted into the right internal jugular vein400 such that the proximal portion 900 p remains positioned within thejugular vein and the distal portion 900 d is positioned within the SVC410. The suction port 926 in the neck region 900 n enables suction ofblood from the right subclavian vein 402, and from the innominate vein403. Such arrangement enables drainage of both the right lymphatic ductand the thoracic duct.

FIG. 29 illustrates another embodiment in which the a covered stent 900′with three tapered sections 900′a, 900′b, 900′c is inserted via the leftinternal jugular vein 407 into the right subclavian vein 402. Thecovered stent 900′ is covered between its two opposite ends with twoopenings 926 a, 926 b which are located in each of the neck sections900′n and another larger opening 926 c, which is located in the middle,larger diameter section 900 b and oriented toward the SVC 410. The bloodflowing through the left internal jugular vein and right subclavian veinis directed into the SVC. The right jugular vein flow and leftsubclavian vein flow are suctioned through the catheter together withflow from both lymphatic vessels, and is return to the vasculatureproximally of the stent into the superior section of the left internaljugular vein. In such an embodiment the stent 900′ can be placed fromeither side (subclavian or jugular vein) to either opposite vessel. Forexample, the stent 900′ can extend between the left jugular vein 407 andright jugular vein 400, or between right jugular vein 400 and the leftsubclavian vein 405. A variety of other positioning combinations arealso possible, depending upon a patient's anatomy, as will be understoodby a person skilled in the art.

In another embodiment, shown in FIG. 30, a stent 840 having a somewhathour glass shape, can be implanted within the left jugular vein 400 inproximity to the subclavian vein 402. As shown, a thinner, centralregion 840 m of the stent is positioned distal to the subclavian vein402 and in proximity to the lymphatic duct entry. The stent 840 includesa lumen 842 extending therethrough to accommodate blood flow and asuction tube 844 having a suction port 846 formed in the thinner,central region 840 m of the stent 840. The suction port 846 and suctiontube 844 are in fluid communication with an external pump (not shown).In use, the entire blood volume is directed into and through the stentand the pump is required to circulate only the lymphatic fluid that iswithdrawn through the suction tube and the suction port.

In an alternate embodiment, one or more restriction stents can beimplanted to create a low pressure region proximate to the lymphaticduct. As shown in FIG. 19, conical stents 504 a, 504 b can be implantedat the outflow junction of the lymphatic duct with the subclavian orjugular vein. The stents 504 a, 504 b can have a first end 504 f with afirst diameter and a second end 504 s with a diameter larger than thefirst diameter. The first end 504 f can be position in the lymphaticjunction thereby creating a lower pressure gradient in the veinproximate to the first end 504 f of the stent than the regulatingcentral venous pressure. Placement of the stent can create a pressuregradient along the lymphatic vessels thereby facilitating drainage fromthe lymphatic vessels. Applying the Bernoulli equation that conservesenergy if the cross section of the flow is reduced, the speed of theflow is increased (A1V1=A2V2). In this embodiment, when the velocity ofthe fluid increases, due to the Bernoulli equation, the pressure mustdrop.

In some embodiments, a kink resistant stent 506 can be implanted in thethoracic duct 508 at the location where the duct makes a 180 degreeturn. The fluid flow can be restricted or impleaded by an obstruction orkink thereby impeding fluid clearance. As shown in FIG. 20, placement ofthe stent can facilitate fluid clearance by maintaining an open passage,thereby enhancing flow back into the venous circulation. In someembodiments, the stent may include a one way valve to prevent backflowof the fluid.

One skilled in the art will appreciate further features and advantagesof the invention based on the above-described embodiments. Accordingly,the invention is not to be limited by what has been particularly shownand described, except as indicated by the appended claims. Allpublications and references cited herein are expressly incorporatedherein by reference in their entirety.

What is claimed is:
 1. A method of treating edema in a subject, themethod comprising: positioning a device in a blood vessel of a subjectin a vicinity of a region of outflow from a thoracic duct and/or alymphatic duct; and operating the device in order to reduce pressure atthe region of outflow from the thoracic duct and/or the lymphatic ductwhile maintaining intravascular pressure of the subject, therebyincreasing flow through the thoracic duct and/or the lymphatic duct, andtreating edema in the subject; wherein operating the device comprisesdeploying from the device at least a first restrictor, the firstrestrictor having the form of a symmetrical inflatable member that, whendeployed, expands uniformly such that when fully deployed, therestrictor does not occupy an entire diameter of the blood vessel withinwhich it is positioned, thereby maintaining the intravascular pressureof the subject.
 2. The method of claim 1, wherein operating the devicefurther comprising operating an impeller proximate the restrictor toreduce the pressure.
 3. The method of claim 2, wherein operating thedevice further comprising deploying a second restrictor, wherein thepressure is reduced between the first restrictor and the secondrestrictor.
 4. The method of claim 3, wherein the first restrictor andthe second restrictor flank the region of outflow from the thoracic ductand/or the lymphatic duct.
 5. The method of claim 1, wherein deployingthe first restrictor is performed without navigational guidance duringthe deploying step.
 6. The method of claim 5, wherein the positioningstep is performed without the use of imaging to position the device inthe vicinity of a region of outflow from a thoracic duct and/or alymphatic duct, and further wherein the method includes deploying thefirst restrictor without the use of imaging after the device ispositioned.
 7. The method of claim 1, further comprising monitoring, viaone or more pressure sensors on the device, fluid pressure within a bodylumen in which the device is deployed and/or within the regionassociated with the thoracic duct and/or lymphatic duct.
 8. The methodof claim 7, wherein the pressure at the region of the thoracic ductand/or lymphatic duct is reduced to at or below 6 mmHg.
 9. A method oftreating edema in a subject, the method comprising: providing a devicecomprising at least one conduit, at least one restrictor and at leastone impeller operably associated with the at least one conduit;positioning the device within a blood vessel of a subject in a regionnear outflow from a thoracic duct and/or a lymphatic duct; and deployingthe at least one restrictor and activating the impeller to create aregion of reduced pressure at the thoracic duct and/or lymphatic ductwhile maintaining intravascular pressure, thereby increasing flowthrough the thoracic duct and/or lymphatic duct and treating edema inthe subject; wherein the at least one restrictor is at least oneselectively inflatable balloon that, when deployed, expands uniformlysuch that when fully deployed, the restrictor does not occupy an entirediameter of the blood vessel within which it is positioned, therebymaintaining the intravascular pressure of the subject.
 10. The method ofclaim 9, wherein the impeller is proximate the restrictor.
 11. Themethod of claim 9, wherein the impeller is distal the restrictor and theconduit tapers from the restrictor toward the impeller.
 12. The methodof claim 9, wherein the device comprises a plurality of restrictors. 13.The method of claim 9, further comprising monitoring, via one or morepressure sensors on the device, fluid pressure within the body lumenand/or within the region associated with the thoracic duct and/orlymphatic duct.
 14. The method of claim 9, wherein the device comprisesa catheter.
 15. The method of claim 14, wherein the catheter comprises adiameter in a range from 8 French to 18 French.